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            "abstractNote": "African trypanosomiases, including the human disease referred to as ‘sleeping sickness’ and the animal diseases such as nagana, surra and dourine, are neglected vector-borne diseases that after years of research still need improved diagnosis and chemotherapy. Advances in proteomics offer new tools to define biomarkers, whose expression may reflect host–parasite interactions occurring during the infection. In this review, the authors first describe the current diagnostic tools used to detect a trypanosome infection during field surveys, and then discuss their interests, limits and further evolutions. The authors also report on the contribution of molecular diagnostics, and the recent advances and developments that make it suitable for fieldwork. The authors then explore the recent uses of proteomics technology to define host and parasite biomarkers that allow detection of the infection, the power and constraints of the technology. The authors conclude by discussing the urgent need to use the biomarkers dis...",
            "publicationTitle": "Expert Review of Proteomics",
            "publisher": "",
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            "issue": "3",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "289-301",
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            "DOI": "10.1586/epr.13.14",
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            "shortTitle": "Proteomics",
            "language": "EN",
            "libraryCatalog": "",
            "callNumber": "",
            "rights": "© 2013 Expert Reviews Ltd",
            "extra": "",
            "tags": [
                {
                    "tag": "Human African trypanosomiasis",
                    "type": 1
                },
                {
                    "tag": "Proteomics",
                    "type": 1
                },
                {
                    "tag": "animal trypanosomosis",
                    "type": 1
                },
                {
                    "tag": "molecular diagnosis",
                    "type": 1
                },
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                    "tag": "serodiagnosis",
                    "type": 1
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            "version": 69,
            "itemType": "journalArticle",
            "title": "PanelomiX: A threshold-based algorithm to create panels of biomarkers",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Xavier",
                    "lastName": "Robin"
                },
                {
                    "creatorType": "author",
                    "firstName": "Natacha",
                    "lastName": "Turck"
                },
                {
                    "creatorType": "author",
                    "firstName": "Alexandre",
                    "lastName": "Hainard"
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                {
                    "creatorType": "author",
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                    "lastName": "Tiberti"
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                    "creatorType": "author",
                    "firstName": "Frédérique",
                    "lastName": "Lisacek"
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                {
                    "creatorType": "author",
                    "firstName": "Jean-Charles",
                    "lastName": "Sanchez"
                },
                {
                    "creatorType": "author",
                    "firstName": "Markus",
                    "lastName": "Müller"
                }
            ],
            "abstractNote": "Abstract \nIn order to increase their predictive power, medical biomarkers can be combined into panels. However, the lack of ready-to-use tools generating interpretable results and implementing rigorous validation standards hampers the more widespread application of panels and their translation into clinical practice. \n \nThe computational toolbox we present here – PanelomiX – uses the iterative combination of biomarkers and thresholds (ICBT) method. This method combines biomarkers and clinical scores by selecting thresholds that provide optimal classification performance. To speed up the calculation for a large number of biomarkers, PanelomiX selects a subset of thresholds and parameters based on the random forest method. The panels’ robustness and performance are analysed by cross-validation (CV) and receiver operating characteristic (ROC) analysis. \n \nUsing 8 biomarkers, we compared this method against classic combination procedures in the determination of outcome for 113 patients with an aneurysmal subarachnoid haemorrhage. The panel classified the patients better than the best single biomarker (p &lt; 0.005) and compared favourably with other off-the-shelf classification methods. \n \nIn conclusion, the PanelomiX toolbox combines biomarkers and evaluates the performance of panels to classify patients better than single markers or other classifiers. The ICBT algorithm proved to be an efficient classifier, the results of which can easily be interpreted.",
            "publicationTitle": "Translational Proteomics",
            "publisher": "",
            "place": "",
            "date": "2013",
            "volume": "1",
            "issue": "1",
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            "pages": "57-64",
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            "journalAbbreviation": "Translational Proteomics",
            "DOI": "10.1016/j.trprot.2013.04.003",
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            "rights": "",
            "extra": "",
            "tags": [
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                    "tag": "Aneurysmal subarachnoid haemorrhage",
                    "type": 1
                },
                {
                    "tag": "Biomarkers",
                    "type": 1
                },
                {
                    "tag": "Clinical study",
                    "type": 1
                },
                {
                    "tag": "Combination of biomarkers",
                    "type": 1
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                    "tag": "Panel",
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            "dateAdded": "2013-06-08T16:17:55Z",
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        "data": {
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            "version": 68,
            "itemType": "journalArticle",
            "title": "Neopterin Is a Cerebrospinal Fluid Marker for Treatment Outcome Evaluation in Patients Affected by Trypanosoma brucei gambiense Sleeping Sickness",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Natalia",
                    "lastName": "Tiberti"
                },
                {
                    "creatorType": "author",
                    "firstName": "Veerle",
                    "lastName": "Lejon"
                },
                {
                    "creatorType": "author",
                    "firstName": "Alexandre",
                    "lastName": "Hainard"
                },
                {
                    "creatorType": "author",
                    "firstName": "Bertrand",
                    "lastName": "Courtioux"
                },
                {
                    "creatorType": "author",
                    "firstName": "Xavier",
                    "lastName": "Robin"
                },
                {
                    "creatorType": "author",
                    "firstName": "Natacha",
                    "lastName": "Turck"
                },
                {
                    "creatorType": "author",
                    "firstName": "Krister",
                    "lastName": "Kristensson"
                },
                {
                    "creatorType": "author",
                    "firstName": "Enock",
                    "lastName": "Matovu"
                },
                {
                    "creatorType": "author",
                    "firstName": "John Charles",
                    "lastName": "Enyaru"
                },
                {
                    "creatorType": "author",
                    "firstName": "Dieudonné",
                    "lastName": "Mumba Ngoyi"
                },
                {
                    "creatorType": "author",
                    "firstName": "Sanjeev",
                    "lastName": "Krishna"
                },
                {
                    "creatorType": "author",
                    "firstName": "Sylvie",
                    "lastName": "Bisser"
                },
                {
                    "creatorType": "author",
                    "firstName": "Joseph Mathu",
                    "lastName": "Ndung′u"
                },
                {
                    "creatorType": "author",
                    "firstName": "Philippe",
                    "lastName": "Büscher"
                },
                {
                    "creatorType": "author",
                    "firstName": "Jean-Charles",
                    "lastName": "Sanchez"
                }
            ],
            "abstractNote": "Author SummaryThe reduction of the number of lumbar punctures performed during the follow-up of patients affected by sleeping sickness (HAT) is considered a research priority. Follow-up, consisting of the examination of cerebrospinal fluid (CSF) for presence of parasites and for the number of leukocytes, is necessary to assess treatment outcome. However, diagnosis of treatment failure is still imperfect and WHO encourages improvements in defining criteria. Many studies have attempted to standardize actual methods and to define a cut-off for the number of white blood cells in CSF to define relapses, while only few have proposed alternatives to current practice. Here we show that neopterin, already proven to be a powerful marker for staging T. b. gambiense HAT, is also useful in evaluating post-therapeutic outcome. The measurement of neopterin concentration in CSF during the follow-up may allow reduction in the number of lumbar punctures from five to three for the majority of cured patients.",
            "publicationTitle": "PLOS Neglected Tropical Diseases",
            "publisher": "",
            "place": "",
            "date": "février 28, 2013",
            "volume": "7",
            "issue": "2",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "e2088",
            "series": "",
            "seriesTitle": "",
            "seriesText": "",
            "journalAbbreviation": "PLoS Negl Trop Dis",
            "DOI": "10.1371/journal.pntd.0002088",
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            "url": "http://dx.doi.org/10.1371/journal.pntd.0002088",
            "accessDate": "2013-03-09T14:42:49Z",
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            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Peter GE",
                    "lastName": "Kennedy"
                }
            ],
            "abstractNote": "Summary \nHuman African trypanosomiasis, or sleeping sickness, is caused by infection with parasites of the genus Trypanosoma, transmitted by the tsetse fly. The disease has two forms, Trypanosoma brucei (T b) rhodesiense and T b gambiense; and is almost always fatal if untreated. Despite a recent reduction in the number of reported cases, patients with African trypanosomiasis continue to present major challenges to clinicians. Because treatment for CNS-stage disease can be very toxic, diagnostic staging to distinguish early-stage from late-stage disease when the CNS in invaded is crucial but remains problematic. Melarsoprol is the only available treatment for late-stage T b rhodesiense infection, but can be lethal to 5% of patients owing to post-treatment reactive encephalopathy. Eflornithine combined with nifurtimox is the first-line treatment for late-stage T b gambiense. New drugs are in the pipeline for treatment of CNS human African trypanosomiasis, giving rise to cautious optimism.",
            "publicationTitle": "The Lancet Neurology",
            "publisher": "",
            "place": "",
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            "section": "",
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            "pages": "186-194",
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            "seriesTitle": "",
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            "DOI": "10.1016/S1474-4422(12)70296-X",
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    {
        "key": "22KZG98K",
        "version": 1,
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            },
            "creatorSummary": "MacLean et al.",
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        "data": {
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            "version": 1,
            "itemType": "journalArticle",
            "title": "Stage Progression and Neurological Symptoms in Trypanosoma brucei rhodesiense Sleeping Sickness: Role of the CNS Inflammatory Response",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Lorna",
                    "lastName": "MacLean"
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                {
                    "creatorType": "author",
                    "firstName": "Hansotto",
                    "lastName": "Reiber"
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                {
                    "creatorType": "author",
                    "firstName": "Peter G. E.",
                    "lastName": "Kennedy"
                },
                {
                    "creatorType": "author",
                    "firstName": "Jeremy M.",
                    "lastName": "Sternberg"
                }
            ],
            "abstractNote": "Author SummaryHuman African trypanosomiasis, caused by the parasites Trypanosoma brucei rhodesiense and T.b.gambiense, is clinically defined by two diagnostic stages, an early stage where the parasites appear to be localised to the blood and lymphatic systems, and a late stage where the parasites are also localised in the central nervous system (CNS) and cause a meningoencephalitis, which is fatal if untreated. We studied the progression between these stages of infection in T.b.rhodesiense infections in Uganda. Progression from early to late stage was associated with an increase in inflammatory responses in the CNS as measured by analysis of the cerebrospinal fluid. However, contrary to predictions based on experimental model studies, neither disease stage progression nor CNS inflammatory responses were directly associated with development of neurological symptoms. Our results suggest that biological basis of the boundary between the two diagnostic stages in this infection may not be clear cut, with implications for therapeutic decision making.",
            "publicationTitle": "PLoS Negl Trop Dis",
            "publisher": "",
            "place": "",
            "date": "octobre 25, 2012",
            "volume": "6",
            "issue": "10",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "e1857",
            "series": "",
            "seriesTitle": "",
            "seriesText": "",
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            "DOI": "10.1371/journal.pntd.0001857",
            "citationKey": "",
            "url": "http://dx.doi.org/10.1371/journal.pntd.0001857",
            "accessDate": "2012-11-05T08:20:04Z",
            "PMID": "",
            "PMCID": "",
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            "shortTitle": "Stage Progression and Neurological Symptoms in Trypanosoma brucei rhodesiense Sleeping Sickness",
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    {
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            "creatorSummary": "Turck et al.",
            "parsedDate": "2012-09-17",
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        "data": {
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            "version": 1,
            "itemType": "journalArticle",
            "title": "Blood Glutathione S-Transferase-π as a Time Indicator of Stroke Onset",
            "creators": [
                {
                    "creatorType": "author",
                    "firstName": "Natacha",
                    "lastName": "Turck"
                },
                {
                    "creatorType": "author",
                    "firstName": "Xavier",
                    "lastName": "Robin"
                },
                {
                    "creatorType": "author",
                    "firstName": "Nadia",
                    "lastName": "Walter"
                },
                {
                    "creatorType": "author",
                    "firstName": "Catherine",
                    "lastName": "Fouda"
                },
                {
                    "creatorType": "author",
                    "firstName": "Alexandre",
                    "lastName": "Hainard"
                },
                {
                    "creatorType": "author",
                    "firstName": "Roman",
                    "lastName": "Sztajzel"
                },
                {
                    "creatorType": "author",
                    "firstName": "Ghislaine",
                    "lastName": "Wagner"
                },
                {
                    "creatorType": "author",
                    "firstName": "Denis F.",
                    "lastName": "Hochstrasser"
                },
                {
                    "creatorType": "author",
                    "firstName": "Joan",
                    "lastName": "Montaner"
                },
                {
                    "creatorType": "author",
                    "firstName": "Pierre R.",
                    "lastName": "Burkhard"
                },
                {
                    "creatorType": "author",
                    "firstName": "Jean-Charles",
                    "lastName": "Sanchez"
                }
            ],
            "abstractNote": "Background. Ability to accurately determine time of stroke onset remains challenging. We hypothesized that an early biomarker characterized by a rapid increase in blood after stroke onset may help defining better the time window during which an acute stroke patient may be candidate for intravenous thrombolysis or other intravascular procedures. \nMethods. The blood level of 29 proteins was measured by immunoassays on 2 independent and prospective cohorts of stroke patients (N=203) and controls (N=119). Mann-Whitney U tests, ROC curves and diagnostic odd ratios were applied to evaluate their clinical performances.\nResults. Among the 29 molecules tested in cohort 1, GST- concentration was the most significantly elevated marker in the blood of stroke patients (p<0.001). More importantly, GST- displayed the best area under the curve (AUC, 0.79) and the best diagnostic odd ratios (10.0) for discriminating early (within the first 3h of stroke onset) vs. late stroke patients (> 3h after onset). Moreover, GST- showed also the highest AUC (0.83) and performances for detecting patients treated with tPA (N=12) compared to ineligible patients (N=103). According to goal-oriented distinct cut-offs (sensitivity(Se)-oriented: 17.7 or specificity(Sp)-oriented: 65.2ug/L), the GST- test obtained 91%Se/50%Sp and 50%Se/91%Sp, respectively. Similar results were obtained in cohort 2. \nConclusions. This study demonstrates that GST-can accurately predict the time of stroke onset in over 50% of early stroke patients. The GST- test could therefore complement current guidelines for tPA administration and potentially increase the number of patients accessing thrombolysis.",
            "publicationTitle": "PLoS ONE",
            "publisher": "",
            "place": "",
            "date": "septembre 17, 2012",
            "volume": "7",
            "issue": "9",
            "section": "",
            "partNumber": "",
            "partTitle": "",
            "pages": "e43830",
            "series": "",
            "seriesTitle": "",
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            "journalAbbreviation": "PLoS ONE",
            "DOI": "10.1371/journal.pone.0043830",
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            "accessDate": "2012-09-21T10:38:12Z",
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            "title": "Cerebrospinal Fluid Neopterin as Marker of the Meningo-Encephalitic Stage of Trypanosoma brucei gambiense Sleeping Sickness",
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                    "creatorType": "author",
                    "firstName": "Natalia",
                    "lastName": "Tiberti"
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                    "firstName": "Alexandre",
                    "lastName": "Hainard"
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                    "firstName": "John Charles",
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                    "creatorType": "author",
                    "firstName": "Xavier",
                    "lastName": "Robin"
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                {
                    "creatorType": "author",
                    "firstName": "Natacha",
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                    "firstName": "Krister",
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                    "firstName": "Dieudonné Mumba",
                    "lastName": "Ngoyi"
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                {
                    "creatorType": "author",
                    "firstName": "Gedeão M. L.",
                    "lastName": "Vatunga"
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                    "firstName": "Sanjeev",
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                    "firstName": "Philippe",
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                    "firstName": "Sylvie",
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                    "creatorType": "author",
                    "firstName": "Joseph Mathu",
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                    "creatorType": "author",
                    "firstName": "Jean-Charles",
                    "lastName": "Sanchez"
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            "abstractNote": "BackgroundSleeping sickness, or human African trypanosomiasis (HAT), is a protozoan disease that affects rural communities in sub-Saharan Africa. Determination of the disease stage, essential for correct treatment, represents a key issue in the management of patients. In the present study we evaluated the potential of CXCL10, CXCL13, ICAM-1, VCAM-1, MMP-9, B2MG, neopterin and IgM to complement current methods for staging Trypanosoma brucei gambiense patients.Methods and FindingsFive hundred and twelve T. b. gambiense HAT patients originated from Angola, Chad and the Democratic Republic of the Congo (D.R.C.). Their classification as stage 2 (S2) was based on the number of white blood cells (WBC) (>5/µL) or presence of parasites in the cerebrospinal fluid (CSF). The CSF concentration of the eight markers was first measured on a training cohort encompassing 100 patients (44 S1 and 56 S2). IgM and neopterin were the best in discriminating between the two stages of disease with 86.4% and 84.1% specificity respectively, at 100% sensitivity. When a validation cohort (412 patients) was tested, neopterin (14.3 nmol/L) correctly classified 88% of S1 and S2 patients, confirming its high staging power. On this second cohort, neopterin also predicted both the presence of parasites, and of neurological signs, with the same ability as IgM and WBC, the current reference for staging.ConclusionsThis study has demonstrated that neopterin is an excellent biomarker for staging T. b. gambiense HAT patients. A rapid diagnostic test for detecting this metabolite in CSF could help in more accurate stage determination.",
            "publicationTitle": "PLoS ONE",
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            "date": "juillet 18, 2012",
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                    "firstName": "Paul F.",
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                    "firstName": "Maria",
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            "abstractNote": "Human African trypanosomiasis (HAT), or sleeping sickness, is a severe disease caused by Trypanosoma brucei (T.b.). The disease hallmark is sleep alterations. Brain involvement in HAT is a crucial pathogenetic step for disease diagnosis and therapy. In this study, a rat model of African trypanosomiasis was used to assess changes of sleep-wake, rest-activity, and body temperature rhythms in the time window previously shown as crucial for brain parenchyma invasion by T.b. to determine potential biomarkers of this event. Chronic radiotelemetric monitoring in Sprague-Dawley rats was used to continuously record electroencephalogram, electromyogram, rest-activity, and body temperature in the same animals before (baseline recording) and after infection. Rats were infected with T.b. brucei. Data were acquired from 1 to 20 d after infection (parasite neuroinvasion initiates at 11–13 d post-infection in this model), and were compared to baseline values. Sleep parameters were manually scored from electroencephalographic-electromyographic tracings. Circadian rhythms of sleep time, slow-wave activity, rest-activity, and body temperature were studied using cosinor rhythmometry. Results revealed alterations of most of the analyzed parameters. In particular, sleep pattern and sleep-wake organization plus rest-activity and body temperature rhythms exhibited early quantitative and qualitative alterations, which became marked around the time interval crucial for parasite neuroinvasion or shortly after. Data derived from actigrams showed close correspondence with those from hypnograms, suggesting that rest-activity could be useful to monitor sleep-wake alterations in African trypanosomiasis.",
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